scholarly journals Model-based detection of putative synaptic connections from spike recordings with latency and type constraints

2020 ◽  
Vol 124 (6) ◽  
pp. 1588-1604
Author(s):  
Naixin Ren ◽  
Shinya Ito ◽  
Hadi Hafizi ◽  
John M. Beggs ◽  
Ian H. Stevenson

Detecting synaptic connections using large-scale extracellular spike recordings is a difficult statistical problem. Here, we develop an extension of a generalized linear model that explicitly separates fast synaptic effects and slow background fluctuations in cross-correlograms between pairs of neurons while incorporating circuit properties learned from the whole network. This model outperforms two previously developed synapse detection methods in the simulated networks and recovers plausible connections from hundreds of neurons in in vitro multielectrode array data.

2020 ◽  
Author(s):  
Naixin Ren ◽  
Shinya Ito ◽  
Hadi Hafizi ◽  
John M. Beggs ◽  
Ian H. Stevenson

AbstractDetecting synaptic connections using large-scale extracellular spike recordings presents a statistical challenge. While previous methods often treat the detection of each putative connection as a separate hypothesis test, here we develop a modeling approach that infers synaptic connections while incorporating circuit properties learned from the whole network. We use an extension of the Generalized Linear Model framework to describe the cross-correlograms between pairs of neurons and separate correlograms into two parts: a slowly varying effect due to background fluctuations and a fast, transient effect due to the synapse. We then use the observations from all putative connections in the recording to estimate two network properties: the presynaptic neuron type (excitatory or inhibitory) and the relationship between synaptic latency and distance between neurons. Constraining the presynaptic neuron’s type, synaptic latencies, and time constants improves synapse detection. In data from simulated networks, this model outperforms two previously developed synapse detection methods, especially on the weak connections. We also apply our model to in vitro multielectrode array recordings from mouse somatosensory cortex. Here our model automatically recovers plausible connections from hundreds of neurons, and the properties of the putative connections are largely consistent with previous research.New & NoteworthyDetecting synaptic connections using large-scale extracellular spike recordings is a difficult statistical problem. Here we develop an extension of a Generalized Linear Model that explicitly separates fast synaptic effects and slow background fluctuations in cross-correlograms between pairs of neurons while incorporating circuit properties learned from the whole network. This model outperforms two previously developed synapse detection methods in the simulated networks, and recovers plausible connections from hundreds of neurons in in vitro multielectrode array data.


2021 ◽  
Author(s):  
Hyemin Han

Research has examined the association between people’s compliance with measures to prevent the spread of COVID-19 and personality traits. However, previous studies were conducted with relatively small-size datasets and employed frequentist analysis that does not allow data-driven model exploration. To address the limitations, a large-scale international dataset, COVIDiSTRESS Global Survey dataset, was explored with Bayesian generalized linear model that enables identification of the best regression model. The best regression models predicting participants’ compliance with Big Five traits were explored. The findings demonstrated first, all Big Five traits, except extroversion, were positively associated with compliance with general measures and distancing. Second, neuroticism, extroversion, and agreeableness were positively associated with the perceived cost of complying with the measures while conscientiousness showed negative association. The findings and the implications of the present study were discussed.


Linguistics ◽  
2015 ◽  
Vol 53 (3) ◽  
Author(s):  
Richard Wiese ◽  
Augustin Speyer

AbstractWords in German show several instances of a seemingly optional schwa-zero alternation, both in relation with inflected forms as well as in the final position of stems and simplex words, as inLarge-scale corpora are used as the main source of evidence for the verification or falsification of the hypothesis. A diverse set of nouns and adverbs involving schwa-zero alternations were studied in appropriate phrasal contexts, both from present-day Standard German and from Early New High German. Based on comprehensive corpus counts, these phrases are tested for the hypothesis of prosodic parallelism. A series of chi square tests and a generalized linear model with mixed effects demonstrate statistically that the prosodic shapes of the target word and its adjacent form are not independent of each other. The focus of the paper is on empirical evidence for


1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.


2020 ◽  
Vol 26 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Edézio F. Cunha-Junior ◽  
Valter V. Andrade-Neto ◽  
John F. Bower ◽  
Guilherme A. M. Jardim ◽  
...  

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.


2020 ◽  
Vol 21 ◽  
Author(s):  
Yin-xue Wang ◽  
Yi-xiang Wang ◽  
Yi-ke Li ◽  
Shi-yan Tu ◽  
Yi-qing Wang

: Ovarian cancer (OC) is one of the deadliest gynecological malignancy. Epithelial ovarian cancer (EOC) is its most common form. OC has both a poor prognosis and a high mortality rate due to the difficulties of early diagnosis, the limitation of current treatment and resistance to chemotherapy. Extracellular vesicles is a heterogeneous group of cellderived submicron vesicles which can be detected in body fluids, and it can be classified into three main types including exosomes, micro-vesicles, and apoptotic bodies. Cancer cells can produce more EVs than healthy cells. Moreover, the contents of these EVs have been found distinct from each other. It has been considered that EVs shedding from tumor cells may be implicated in clinical applications. Such as a tool for tumor diagnosis, prognosis and potential treatment of certain cancers. In this review, we provide a brief description of EVs in diagnosis, prognosis, treatment, drug-resistant of OC. Cancer-related EVs show powerful influences on tumors by various biological mechanisms. However, the contents mentioned above remain in the laboratory stage and there is a lack of large-scale clinical trials, and the maturity of the purification and detection methods is a constraint. In addition, amplification of oncogenes on ecDNA is remarkably prevalent in cancer, it may be possible that ecDNA can be encapsulated in EVs and thus detected by us. In summary, much more research on EVs needs to be perform to reveal breakthroughs in OC and to accelerate the process of its application on clinic.


2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.


2021 ◽  
Author(s):  
Marion Germain ◽  
Daniel Kneeshaw ◽  
Louis De Grandpré ◽  
Mélanie Desrochers ◽  
Patrick M. A. James ◽  
...  

Abstract Context Although the spatiotemporal dynamics of spruce budworm outbreaks have been intensively studied, forecasting outbreaks remains challenging. During outbreaks, budworm-linked warblers (Tennessee, Cape May, and bay-breasted warbler) show a strong positive response to increases in spruce budworm, but little is known about the relative timing of these responses. Objectives We hypothesized that these warblers could be used as sentinels of future defoliation of budworm host trees. We examined the timing and magnitude of the relationships between defoliation by spruce budworm and changes in the probability of presence of warblers to determine whether they responded to budworm infestation before local defoliation being observed by standard detection methods. Methods We modelled this relationship using large-scale point count surveys of songbirds and maps of cumulative time-lagged defoliation over multiple spatial scales (2–30 km radius around sampling points) in Quebec, Canada. Results All three warbler species responded positively to defoliation at each spatial scale considered, but the timing of their response differed. Maximum probability of presence of Tennessee and Cape May warbler coincided with observations of local defoliation, or provided a one year warning, making them of little use to guide early interventions. In contrast, the probability of presence of bay-breasted warbler consistently increased 3–4 years before defoliation was detectable. Conclusions Early detection is a critical step in the management of spruce budworm outbreaks and rapid increases in the probability of presence of bay-breasted warbler could be used to identify future epicenters and target ground-based local sampling of spruce budworm.


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